JP 11130750 describes amongst others, substituted phenylaminocarbonylindolyl derivatives as 5-HT receptor antagonists.
EP1129074 describes anthranilic acid amides as inhibitors of vascular endothelial growth factor receptors (VEGFR) and useful in the treatment of angiogenic disorders. WO01/42224 provides carboxyamido derivatives for the treatment of Alzheimer disease. EP1317443 discloses tricyclic tert-amine derivatives, useful as chemokine receptor CXCR4 or CCR5 modulators for treating human immunodeficiency virus and feline immunodeficiency virus.
EP1379239 discloses N-(2-arylethyl)benzylamines as antagonists of the 5-HT6 receptor. WO00/15357 provides piperazine-4-phenyl derivatives as inhibitors of the interaction between MDM2 and p53. EP1137418 provides tricyclic compounds for restoring conformational stability of a protein of the p53 family. WO03/040402 provides compounds that inhibit the interactions between proteins, such as the interaction between MDM2 and p53. EP1443937 describes substituted 1,4-benzodiazepines and the uses thereof as inhibitors of the MDM2-p53 interactions. EP1458380 provides cis-2,4,5-triphenyl-imidazolones that inhibit the interaction of MDM2 protein with p53-like peptides and have antiproliferative activity.
EP1519932 discloses bisarylsulfonamide compounds that bind to MDM2 and can be used in cancer therapy.
WO2006/032631, WO2007/107543, WO2007/107545, WO2009/019274, WO2009/037308 and WO2009/037343 disclose inhibitors of the interaction between MDM2 and p53.
There is a need for effective small molecules that have potent inhibitory effect against tumor cell growth, have a broad safety profile, and less undesired side effects.
The compounds of the present invention show excellent in-vitro activity and excellent in vivo anti tumor effects. They have low affinity for the P450 enzymes which reduces the risk of adverse drug-drug interaction allowing for a wider safety margin. Moreover, the compounds of the present invention have low drug induced neurological effects and have an improved cardiovascular profile which may favorably influence the dose limiting toxicity of the compounds.